Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer
cell migration in vitro as well as its growth and metastasis in vivo.

Abstract

Delta(9)-Tetrahydrocannabinol (THC) is the primary cannabinoid of marijuana and has
been shown to either potentiate or inhibit tumor growth, depending on the type of
cancer and its pathogenesis. Little is known about the activity of cannabinoids like
THC on epidermal growth factor receptor-overexpressing lung cancers, which are often
highly aggressive and resistant to chemotherapy. In this study, we characterized the
effects of THC on the EGF-induced growth and metastasis of human non-small cell lung
cancer using the cell lines A549 and SW-1573 as in vitro models. We found that these
cells express the cannabinoid receptors CB(1) and CB(2), known targets for THC action,
and that THC inhibited EGF-induced growth, chemotaxis and chemoinvasion. Moreover,
signaling studies indicated that THC may act by inhibiting the EGF-induced phosphorylation
of ERK1/2, JNK1/2 and AKT. THC also induced the phosphorylation of focal adhesion
kinase at tyrosine 397. Additionally, in in vivo studies in severe combined immunodeficient
mice, there was significant inhibition of the subcutaneous tumor growth and lung metastasis
of A549 cells in THC-treated animals as compared to vehicle-treated controls. Tumor
samples from THC-treated animals revealed antiproliferative and antiangiogenic effects
of THC. Our study suggests that cannabinoids like THC should be explored as novel
therapeutic molecules in controlling the growth and metastasis of certain lung cancers.